Computer image of the MRSA bacteria Staphylococcus aureus, which can be extremely hard to treat even with powerful antibiotics.
Photograph: Sebastian Kaulitzki/Science Photo Library/Corbis

A precision drug therapy that wipes out bugs that hide in the body could help clear up persistent infections that do not respond to standard antibiotics.

The treatment works by tagging antibiotics onto antibodies which home in on pathogens and deliver a lethal dose of drug directly to the heart of the infected tissues.

The strategy could transform the treatment of patients with recurring bacterial infections, such as the hospital superbug MRSA, which can be extremely hard to treat even with powerful antibiotics. The approach also raises hopes for treating relapses in tuberculosis patients, and chronic infections that can take hold after heart surgery.

Tests in animals showed that the radical combination, called an antibody-antibiotic conjugate (AAC), was far more effective at clearing up Staphylococcus aureus infections than the frontline antibiotic, vancomycin. “This is about clearing infections more completely,” said Sanjeev Mariathasan, an immunologist who led the work at Genentech in San Francisco.

Wolf-Dietrich Hardt, a microbiologist at the Swiss Federal Institute of Technology in Zurich, who was not involved in the study, said the strategy could slow the emergence of antibiotic resistance because only the targeted bacteria are exposed to the drug, and reduce the harm that antibiotics inflict on healthy microbes that live in the gut.

In April, a government forecast warned that 80,000 people could be killed by an outbreak of drug-resistant infections in Britain.

While some Staphylococcus aureus infections are hard to treat because the bugs are drug-resistant, others are tough to clear because the bugs appear to take cover inside cells in the body. Many drugs cannot get into the cells, or do not work once they get there.

To tackle the hiding pathogens, Mariathasan’s team took antibodies that recognise all strains of Staphylococcus aureus, and hooked them up via a chemical bridge to powerful antibiotics, similar to the drug rifampicin. The bridge was designed to break when it comes into contact with enzymes that bugs encounter when they infect cells. This way the drug is only released, and only effective, when the bugs try to run for cover.

In tests reported in the journal Nature, Mariathasan showed that injections of the antibody-drug combination into infected mice wiped out Staphylococcus aureus infections far more effectively than antibiotics alone. “We’d love to now test this in humans,” he said.

In an accompanying article in Nature, Hardt writes that the strategy was “strikingly more potent” than standard drugs.

“Compared with conventional antibiotic therapy, the prodrug approach is likely to reduce both the emergence of antibiotic resistance (by reducing the exposure of other bacteria to the active drug), and the disruption of the body’s normal communities of microorganisms,” he notes.

The use of antibodies to deliver antibiotics directly to specific infectious bugs has also raised hopes that promising antibiotics that never made it to market because they are too toxic or not potent enough in the body, could be resurrected.

“We have so many active drugs against Staph out there, but they never see the light of day because they don’t have all the properties a drug needs,” Mariathasan said. “You might need to dose high, and that causes toxicity, so they kill bugs superbly, but they also cause damage to the host’s cells. This way you can put in 1/100th of that molecule and target it to the sites of infection. It’s another way to repurpose some of these previously shelved antibiotics.”